Dramatic morphological and cytological effects that include ruffling, rounding, and fluid-phase pinocytosis occur in the human epidermoid cell line A431 in response to epidermal growth factor (EGF), as well as several biochemically defined stimulations, such as protein phosphorylation. The extraordinarily high number (2-3X10 to the 6th power) of EGF receptors facilitates biochemical and cytological examination of hormone/receptor binding, clustering, internalization, and hormone fate through studies with 125I-EFG and F:EGF (greater than 99 percent specific monomeric ferritin derivative of EGF). Those dynamic responses provide a highly active system in which, with electron microscopy, we propose to investigate: (1) cytological aspects of the hormone response; (2) movement of macromolecules in the plane of the membrane, clustering, adsorptive pinocytosis; (3) cell surface augmentation, interchange among organelles and membrane compartments; (4) synthesis and insertion of macromolecules into the plasmalemma. More specifically, our goals for the current year have been to further our understanding in the A431 cell response to EGF with regard to (a) cell surface augmentation, (b) cytoskeletal changes, and (c) movement of the EGF/receptor complex in the plane of the membrane.